A Toxicological Profile by the U.S. Dept. of
Health and Human Services, Public Health Service, Agency for
Toxic Substances and Disease Registry (ATSDR) TP-91/17, Page 112,
Sec. 2.7 (Health Impacts), April 1993

POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE

Existing data indicate that subsets of the population may be
unusually susceptible to the toxic effects of fluoride and its
compounds. These populations include the elderly, people with
deficiencies of calcium, magnesium, and/or vitamin C, and people
with cardiovascular and kidney problems.

Because fluoride is excreted through the kidney, people with
renal insufficiency would have impaired renal clearance of
fluoride (Juncos and Donadio 1972). Fluoride retention on a
low-protein, low-calcium, and low-phosphorus diet was 65% in
patients with chronic renal failure, compared with 20% in normal
subjects (Spencer et al. 1980a). Serum creatinine levels were
weakly correlated (r=0.35-0.59) with serum fluoride levels
(Hanhijarvi 1982). People on kidney dialysis are particularly
susceptible to the use of fluoridated water in the dialysis
machine (Anderson et al. 1980). This is due to the decreased
fluoride clearance combined with the intravenous exposure to
large amounts of fluoride during dialysis. Impaired renal
clearance of fluoride has also been found in people with diabetes
mellitus and cardiac insufficiency (Hanhijarvi 1974). People over
the age of 50 often have decreased renal fluoride clearance
(Hanhijarvi 1974). This may be because of the decreased rate of
accumulation of fluoride in bones or decreased renal function.
This decreased clearance of fluoride may indicate that elderly
people are more susceptible to fluoride toxicity.

Poor nutrition increases the incidence and severity of dental
fluorosis (Murray and Wilson 1948; Pandit et al. 1940) and
skeletal fluorosis (Pandit et al. 1940). Comparison of dietary
adequacy, water fluoride levels, and the incidence of skeletal
fluorosis in several villages in India suggested that vitamin C
deficiency played a major role in the disease (Pandit et al.
1940). Calcium intake met minimum standards, although the source
was grains and vegetables, rather than milk, and bioavailability
was not determined. Because of the role of calcium in bone
formation, calcium deficiency would be expected to increase
susceptibility to effects of fluoride. No studies in humans
supporting this hypothesis were located. Calcium deficiency was
found to increase bone fluoride levels in a two-week study in
rats (Guggenheim et al. 1976) but not in a 10-day study in
monkeys (Reddy and Srikantia 1971). Guinea pigs administered
fluoride and low-protein diet had larger increases in bone
fluoride than those given fluoride and a control diet (Parker et
al. 1979). Bone changes in monkeys following fluoride treatment
appear to be more marked if the diet is deficient in protein or
vitamin C, but the conclusions are not definitive because of
incomplete controls and small sample size (Reddy and Srikantia
1971). Inadequate dietary levels of magnesium may affect the
toxic effects of fluoride. Fluoride administered to
magnesium-deficient dogs prevented soft-tissue calcification, but
not muscle weakness and convulsions (Chiemchaisri and Philips
1963). In rats, fluoride aggravated the hypomagnesemia condition,
which produced convulsive seizures. The symptoms of magnesium
deficiency are similar to those produced by fluoride toxicity.
This may be because of a fluoride-induced increase in the uptake
of magnesium from plasma into bone.

Some people with cardiovascular problems may be at increased
risk of fluoride toxicity. Fluoride inhibits glycolysis by
inhibiting enolase (Guminska and Sterkowicz 1975; Peters et al.
1964). It also inhibits energy metabolism through the
tricarboxylic acid cycle by blocking the entry of pyruvate and
fatty acids and by inhibiting succinic dehydrogenase (Slater and
Bonner 1952).